Lipid‐lowering effect of mangiferin through the inhibition of pancreatic lipase activity

Abstract Background The inhibition of pancreatic lipase activity to reduce dietary lipid absorption is an effective strategy to combat obesity. Mangiferin, a bioactive flavonoid derived from Mangifera indica , exhibits potent lipid‐lowering potential. However, although its in vitro inhibitory effect on pancreatic lipase has been identified, the underlying mechanism remains poorly understood. Direct in vivo evidence of its impact on dietary lipid absorption is also lacking. This study aimed to elucidate the mechanism of mangiferin's inhibition of pancreatic lipase through in vitro inhibitory kinetics assays and in silico molecular docking analysis. Its effects on dietary lipid absorption were also evaluated in a mouse model of high‐fat diet (HFD)‐induced obesity. Results Inhibitory kinetics assays demonstrated that mangiferin inhibited pancreatic lipase in a reversible, non‐competitive manner, with a half‐ maximal inhibitory concentration (IC 50 ) of 82.31 μmol L −1 . Molecular docking showed that mangiferin bound to the enzyme's allosteric site through hydrogen bonds with Glu‐188, Arg‐191, Gln‐22, and Val‐21 residues, consistent with non‐competitive inhibition. In vivo studies revealed that administration of 200 mg kg −1 body weight of mangiferin alleviated HFD‐induced obesity, hepatic steatosis, and hyperlipidemia significantly. Notably, mangiferin increased fecal lipid excretion by 52.5%, which was significant, indicating reduced dietary lipid absorption. Conclusion These findings suggest that mangiferin is a promising pancreatic lipase inhibitor, which may reduce dietary lipid absorption, contributing, at least partially, to its lipid‐lowering effects. © 2025 Society of Chemical Industry.